Degenkolb, of Team-Giant, finished nearly a bike’s length ahead of defending champion Alexander Kristoff of Norway, with Australian Michael Matthews completing the podium in a time of 6hr 46min.
It was Degenkolb’s maiden Milan-SanRemo title but he becomes the second German in three races to triumph, following from Gerald Ciolek’s 2013 win.
“It’s really a fantastic moment,” a delighted Degenkolb told Rai Sport.
“The race happened exactly as we hoped it would. I really love this place… four years in a row I’ve been here trying to win this race.
“I know the course, and the Via Roma, it’s special to win here. It’s amazing.”
The result was the biggest win of Degenkolb’s career and should establish him as one of the top one-day classic specialists.
Already last year he finished second at Paris-Roubaix and won Ghent-Wevelgem, while he was ninth at September’s World Championships, having finished fourth the year before.
While not an out-and-out sprinter, he’s the type of sprinter-puncher who comes into his own when the finish to a race proves too lumpy for true sprinters.
– Small advantage –
The 26-year-old won four stages at last year’s Vuelta a Espana and five on the 2012 edition, while he also won one stage at the 2013 Giro d’Italia.
An 11-man breakaway provided some early drama in the season’s first of five ‘monuments’ but after building a lead of just over ten minutes, their bid would gradually fritter away.
They were reeled in before the final, decisive, climbs of the Cipressa and Poggio set the scene for a number of breakaway attempts which ultimately came to nothing.
Welshman Geraint Thomas was one of three Team Sky riders who pulled away from the main bunch on the Cipressa and when they were joined by five other riders they went on to build a small advantage.
But counter-attacks by BMC and then Etixx rider Zdenek Stybar ultimately brought the peloton back together with 24.5km remaining.
Their pace on the way to the summit left several big names hanging off the back of the peloton, with Kristoff and Britain’s Mark Cavendish, the 2009 champion, looking in trouble.
Although Italy’s last race winner, Filippo Pozzato, pushed the pace on the descent, an attack by BMC’s Daniel Oss tempted Thomas into another counter.
With the final climb, the Poggio, still to come, the pair managed to build their lead on the peloton to 30sec but they were never allowed to break free.
They started the ascent with a 17sec lead and, soon after, Thomas took things into his own hands when he drove away from Oss to go it alone.
Thomas’s effort, however, was over with 4.6km to go as the peloton began the winding descent towards the finish line on Via Roma.
On the 400m long home straight, Kristoff was pushed into launching his sprint with 300 metres to go.
Degenkolb, on the left of the Norwegian’s wheel, bided his time before hitting top speed in the closing 100 metres to win convincingly.
“At first I thought I had no chance of winning this race because the sprint went really early,” said Degenkolb.
“Kristoff was really strong but he started to sprint early and it was just a little bit too long for him. I was lucky he died just before the finish line so I managed to overtake him.”
Results from the opening Spring Classic of 2015, the 293km Milan-San Remo, on Sunday:
1. John Degenkolb (GER/Giant) 6hr 46min 16sec, 2. Alexander Kristoff (NOR/KAT) same time, 3. Michael Matthews (AUS/ORI) s.t., 4. Peter Sagan (SVK/TIN) s.t., 6. Nacer Bouhanni (FRA/COF) s.t., 7. Fabian Cancellara (SUI/TRE) s.t., 8. Davide Cimolai (ITA/LAM) s.t., 9. Tony Gallopin (FRA/LOT) s.t., 10. Edvald Boasson Hagen (NOR/MTN) s.t.
11. Juergen Roelandts (BEL/LOT) s.t., 12. Matti Breschel (DEN/TIN) s.t., 13. Ben Swift (GBR/SKY) s.t., 14. Sebastian Langeveld (NED/CAN) s.t., 15. Tim Wellens (BEL/LOT) s.t., 16. Grega Bole (SLO/CCC) s.t., 17. Paul Martens (GER/LNL) s.t., 18. Sonny Colbrelli (ITA/BAR) s.t., 19. Greg Van Avermaet (BEL/BMC) s.t., 20. Alejandro Valverde (ESP/MOV) s.t.
45. Vincenzo Nibali (ITA/AST) at 23sec, 46. Mark Cavendish (GBR/ETI) s.t., 67. Michal Kwiatkowski (POL/ETI) 4:56.
– Agence France-Presse